©2019 by Dwi U. Kemaladewi.

  • Twitter - White Circle

DEVELOPMENT OF THERAPEUTIC GENOME ENGINEERING IN RARE GENETIC DISEASES

A disease is defined as rare when it affects <200,000 people in the US, or 1 in 2000 people in the EU. Although one rare disease may affect a handful of individuals, the opportunities to have an immediate clinical impact and generate new scientific knowledge make the study of rare genetic conditions greatly valuable and endlessly rewarding. To this end, genome engineering technology has emerged as a powerful tool in the study of rare disease and therapeutic development.

 

We have previously utilized CRISPR/Cas9 technology to correct an underlying mutation and upregulate a compensatory gene in LAMA2-CMD, a rare congenital muscular dystrophy (Kemaladewi et al, Nat Medicine, 2017Kemaladewi, Bassi et al, Nature, 2019). In addition, we have identified imbalanced polyamine metabolism as a novel disease-modifying factor in LAMA2-CMD (Kemaladewi et al , Hum Mol Gen, 2018).

 

We will further evaluate the safety and efficacy of these strategies, with the goal of moving them closer to clinical applications. Furthermore, using LAMA2-CMD as a starting point, we will apply the technology and knowledge we gained to a variety of rare genetic conditions with no available treatment.

 

Get in touch with Dwi for more details about projects.

INTERPLAY BETWEEN SKELETAL MUSCLE & NERVE PATHOPHYSIOLOGY IN NEUROMUSCULAR DISORDERS

Neuromuscular disorders primarily affect skeletal muscles; however, there is a clear involvement and contribution of tissues beyond skeletal muscles to the clinical heterogeneity.  For example, the lack of functional LAMA2 in congenital muscular dystrophy leads to not only myopathy, but also peripheral neuropathy. Yet, it remains underexplored in terms of basic etiology and therapeutic development.

Using a combination of transgenic mouse,  cellular model, viral vector and CRISPR/Cas9 technologies, we seek to understand the origin of peripheral neuropathy and its contribution to skeletal muscle pathology. In addition, we will investigate and characterize novel genetic modifiers involved in myelination defect in the peripheral nervous system. 

 

Get in touch with Dwi for more details about projects.